The burden of malaria is greatest in children and pregnant women in sub-Saharan Africa. Malaria is one of the most important infectious diseases in the world. Uganda reports among the highest transmission intensities in the world. Children and pregnant women are the most vulnerable populations. HIV is also reported at high rates for these populations. If malaria and HIV require treatment at the same time, there is a high risk for drug-drug interactions. This study will:

Determine if the use of anti-HIV medications including lopinavir/ritonavir (LPV/r), nevirapine (NVP) and efavirenz (EFV) will affect the pharmacokinetic (PK) exposure of antimalarial medications (specifically artemether-lumefantrine, AL) during the treatment for uncomplicated malaria in HIV-infected children and pregnant women, and

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:

Primary outcome measurement is the area under the plasma concentration versus time curve for all drug analytes. [ Time Frame: At time of the last dose of a 6 dose regimen and up to 42 days of F/U ] [ Designated as safety issue: No ]

Pharmacokinetic exposure for the antimalarial medication is estimated through sparse or intensive blood sampling around the last dose and for several days following the last dose.

Secondary Outcome Measures:

Malaria reinfection (recrudescence or new infection) [ Time Frame: From Day 0 to 42 days of F/U when using artemether-lumefantrine for uncomplicated malaria ] [ Designated as safety issue: No ]

The association between PK exposure and malaria reinfection is the main secondary outcome.

Parasite clearance rate [ Time Frame: Days 0 to 42 of follow-up ] [ Designated as safety issue: No ]

To assess the relationship between artemisinin exposure and parasite clearance

To assess the relationship between artemether, lumefantrine and antiretroviral exposure and toxicity, particularly neutropenia

Biospecimen Retention: Samples With DNA

Samples are for drug level measurements,parasite density. RNA samples are for host transcriptional and molecular markers of resistance. Samples are also retained for future use including possible genetic testing for drug metabolism variants

HIV infected and uninfected children and pregnant women residing in Tororo, Uganda and receiving care at local health care facilities including the Tororo District Hospital (TDH), perinatal facilities, HIV clinics and the IDRC research clinic. HIV uninfected children, pregnant women and non-pregnant adults also enrolled through TDH, perinatal facilities or other area clinics. Each participant can enroll at the time they present to one of the clinics with uncomplicated malaria

Criteria

Inclusion Criteria:

ALL PARTICIPANTS

Residency within 60 km of the study clinic

Agreement to come to clinic for all follow-up clinical and PK evaluations

Provision of informed consent

HIV-INFECTED PARTICIPANTS

Children:

1) Enrollment in Promote I or meets enrollment criteria and recruited from TDH/TASO or other referral site

6 months to 8 years of age

Weight ≥6 kg

Confirmed HIV infection (positive rapid HIV test to be confirmed by Western Blot or HIV RNA after enrollment)

On a stable ART regimen for at least 10 days prior to enrollment

If co-enrolled from PROMOTE, willingness to undergo intensive PK sampling during a single episode of uncomplicated malaria, and/or population PK/parasite clearance time studies during multiple episodes of uncomplicated malaria.

If enrolled from TDH, willingness to undergo intensive PK sampling during a single episode of malaria or population PK/parasite clearance time studies during episodes of uncomplicated malaria.

Pregnant women

Enrollment in Promote Project 2 or meets enrollment criteria and recruited from TDH/TASO or other referral site

Confirmed HIV infection (positive rapid HIV test to be confirmed by Western Blot or HIV RNA after enrollment)

16 years of age or older

Estimated gestational age between 12 and 38 weeks by last menstrual period and report of quickening

Willingness to undergo intensive PK sampling during episodes of uncomplicated malaria during pregnancy.

HIV UNINFECTED PARTICIPANTS

Children:

Enrollment from TDH or other referral site

6 months to 8 years of age

Weight ≥6 kg

Confirmed HIV negative test (negative rapid HIV test to be confirmed by Western Blot or HIV RNA after enrollment)

Presentation with uncomplicated falciparum malaria as indicated by positive smear for malaria parasites along with clinical evidence of infection (fever or history of fever in the past 24 hours) with planned treatment with AL.

7) Willingness to undergo intensive PK sampling during a single episode of malaria or population PK/parasite clearance time studies during episodes of uncomplicated malaria.

Non-pregnant adults:

Age ≥ 16 years

Confirmed HIV negative test (negative rapid HIV test to be confirmed by Western Blot or HIV RNA after enrollment).

Presentation with uncomplicated falciparum malaria as indicated by positive smear for malaria parasites along with clinical evidence of infection (fever or history of fever in the past 24 hours) with planned treatment with AL.

Negative pregnancy test

Willingness to undergo intensive PK sampling during treatment for a single episode of uncomplicated malaria

Pregnant women:

Age ≥ 16 years

Confirmed HIV negative test (negative rapid HIV test to be confirmed by Western Blot or HIV RNA after enrollment)

Estimated gestational age between 12 and 38 weeks by last menstrual period and report of quickening

Presentation with uncomplicated malaria as indicated by positive smear for malaria parasites along with clinical evidence of infection (fever or history of fever in the past 24 hours) with planned treatment with AL.

No evidence of imminent delivery or threatened abortion at the time of presentation with malaria.

Willingness to undergo intensive PK sampling during episodes of uncomplicated malaria during pregnancy.

Exclusion Criteria:

History of significant comorbidities such as malignancy, active tuberculosis or other WHO stage 4 disease

Current infection with non-falciparum species

Receipt of any medications known to affect cytochrome p450 (CYP450) metabolism (except ART) within 14 days of study enrollment (see 4.2.2)

Signs or evidence of complicated malaria, defined as unarousable coma OR ANY TWO OF THE FOLLOWING SYMPTOMS: Recent febrile convulsions, altered consciousness, lethargy, unable to drink, unable to stand/sit due to weakness, severe anemia (Hb < 5.0 gm/dL), respiratory distress, jaundice

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01717885